This is a Phase 3, multicenter, randomized and double-blind study assessing the interchangeability between TRS003 and China-approved Bevacizumab® (also called China-approved Avastin) for first-line treatment of patients with metastatic Colorectal Cancer (CRC), approximately 126 patients will be enrolled in this study. Patients who sign the informed consent, meet the eligibility criteria and are confirmed as non-progressors after lead-in treatment period with Bevacizumab® in combination with modified FOLFOX6 chemotherapy for 6 cycles, will be randomized (1:1) to either the non-switching arm and receive Bevacizumab® + modified FOLFOX6 for all subsequent cycles or to the switching arm and receive TRS003 alternating with Bevacizumab® in combination with mFOLFOX6 until disease progression or intolerability.

This is a randomized, double-blind Phase 3 clinical trial evaluating the interchangeability, by a comparison of PK parameters between non-Switching and the Switching arms following the final switch between TRS003 and Bevacizumab® in patients with metastatic adenocarcinoma of the colon or rectum (please note that Bevacizumab® means China-approved Bevacizumab® in this protocol, unless otherwise specified). Approximately 126 patients will be enrolled in this study. Patients who sign the informed consent, meet the eligibility criteria and are confirmed as non-progressors after lead-in treatment period with Bevacizumab® in combination with modified FOLFOX6 chemotherapy for 6 cycles, will be randomized (1:1) to either the non-switching arm and receive Bevacizumab® + modified FOLFOX6 for all subsequent cycles or to the switching arm and receive TRS003 alternating with Bevacizumab® in combination with mFOLFOX6 until disease progression or intolerability. There will be 3 switches as detailed in the Treatment section (below) and the Schema. If oxaliplatin-induced neurotoxicity requires discontinuation of oxaliplatin, treatment will continue using leucovorin (LCV) plus 5-fluorouracil (5-FU) in combination with either Bevacizumab® or TRS003 until progressive disease (PD), intolerability, or other cause for stopping treatment.

Inclusion Criteria:

1. Histologically documented adenocarcinoma of the colon or rectum

2. Must have radiographic documentation of measurable metastatic disease (per RECIST v1.1)

3. Patients with resected primary tumors are eligible if documented metastatic disease is present.

4. Age ≥ 18 years

5. ECOG Performance Status of 0-1

6. Patients who received oxaliplatin/fluorouracil-based adjuvant chemotherapy then developed metastatic disease are eligible if > 12 months since last adjuvant chemotherapy treatment. Consider biopsy to confirm lesions are metastatic colorectal cancer, especially if initial CRC was stage I.

7. May have received radiation with radio-sensitizing chemotherapy if completed > 12 months before enrollment. Patients with rectal cancer who have received locoregional radiation therapy are eligible if they have measurable metastatic disease that is outside the radiation therapy portal.

8. Patients with left or right sided primary colon cancers are eligible as are patients with RAS or BRAF mutant tumor (molecular determination is not required).

9. Hypertension must be well controlled (< 150/90) on a stable anti-hypertensive regimen.

10. Patients on full-dose anticoagulation or taking anti-platelet agents are eligible if on a stable dose of medication and have no active bleeding or conditions that predispose to bleeding.

11. For women of childbearing potential, must consent to use two highly effective methods (i.e., total abstinence, placement of an intrauterine device) of contraception during treatment and for an additional 90 days after the last administration of study drug.

    Men with a partner of childbearing potential, must consent to use two highly effective methods of contraception during treatment and for an additional 90 days after the last administration of study drug.

12. Required laboratory values:

    • Granulocytes ≥ 1500/uL
    • Hemoglobin ≥ 9.0 grams/dL
    • Platelets ≥ 100,000/uL
    • Serum creatinine < 1.5 × ULN or calculated creatinine clearance (CLcr) > 50 mL/min.
    • Total bilirubin ≤ 1.5 × upper limit of normal (ULN) except for patients with Gilbert's syndrome, who are included if total bilirubin is < 3 × ULN or if direct bilirubin is < 1.5 × ULN.
    • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN. For those with hepatic metastases, AST and ALT ≤ 5 × ULN.
    • Albumin ≥ 2.5 g/dL
    • Urinalysis ≤ 1+ protein. Patients that have ≥ 2+ proteinuria must have < 1g of protein on a 24h urine collection.

Exclusion Criteria:

1. Prior systemic or regional treatment for metastatic disease
2. Prior exposure to drugs that target VEGF or VEGF receptors (e.g., tyrosine kinase inhibitors, monoclonal antibodies, or soluble receptors).
3. Patients whose tumors have microsatellite instability-high or mismatch repair deficiency
4. Radiotherapy to greater than 25% of the bone marrow. Standard adjuvant rectal cancer chemoradiation will not exclude the patient.
5. Previous or concurrent malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer that the patient has been disease-free for 5 years
6. Sensory or peripheral neuropathy of ≥ grade 2 at baseline
7. Known central nervous system metastases or carcinomatous meningitis
8. Interstitial pneumonia or medically significant interstitial fibrosis of the lung
9. Pleural effusion or ascites that causes ≥ grade 2 dyspnea.
10. Colon or small bowel disorders with baseline symptoms including 3 watery or soft stools per day (patients without colostomy or ileostomy; patients with stoma may be entered at Investigator's discretion).
11. Uncontrolled seizure disorder or active neurological disease
12. Current congestive heart failure (NY Heart Association Class II, III, or IV)
13. Significant hemorrhagic events within 6 months prior to the study screening including hemoptysis > 2.5 mL of red blood, gastrointestinal bleeding, hematemesis, central nervous system hemorrhage, severe epistaxis or vaginal bleeding, etc.
14. Venous or arterial thrombotic events within 6 months of enrollment, including pulmonary embolism or deep vein thrombosis, transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI) requiring surgical or medical intervention. Patients with clinically significant peripheral vascular disease or any other arterial thrombotic event are ineligible.
15. Serious or non-healing wound, ulcer, or bone fracture.
16. Any major surgical procedure within 28 days prior to screening or anticipated elective surgery during the study. Any minor surgery such as central vein catheterization within 48 hours prior to the first dose of the study drugs.
17. Hypersensitivity to Chinese hamster ovary cell products or to recombinant human or murine antibodies.
18. Hypersensitivity to oxaliplatin or any other platinum-based drug.
19. Active hepatitis B or hepatitis C virus. Patients with evidence of infection with hepatitis B who have an undetectable viral load are eligible for study entry. Patients with evidence of infection with hepatitis C should have completed curative therapy.
20. History of HIV infection.
21. Pregnant or breast-feeding females
22. Any uncontrolled intercurrent illness or condition that in the judgement of the Investigator may endanger the patient.

This is a double-blind study. Neither the subjects, nor the Investigator, nor the Sponsor knows which drug is being administered to which group. Only the Biostatistician who generated the actual randomization scheme with IWRS and the Pharmacist or nurse at the study center who prepares the study drugs and dose for the subjects will be unblinded. All other study related individuals including ancillary clinical staff, biological laboratory staff, clinical research associates, medical monitors, and scientific operation and management team at the study center will remain blinded to the treatment assignment.