The goal of this clinical trial is to learn about the efficacy and safety of Fruquintinib with mFOLFOX6/FOLFIRI in patients with mCRC. The main question it aims to answer is:

The conversion surgery rate of the therapy mentioned above. The ORR, R0 surgery rate, DCR, PFS, OS, and safety will be evaluated.

Inclusion Criteria:

1. Provide written informed consent to participate in the study voluntarily.

2. Male or female aged 18-75.

3. Metastatic colorectal adenocarcinoma confirmed by histology or cytology.

4. Have not received systematic anti-tumor therapy before; Patients who have received neoadjuvant/adjuvant therapy may be screened from the time of last chemotherapy to recurrence or progression more than 6 months.

5. RAS/BRAF mutation status and UGT1A1*28/*6 gene polymorphism typing should be determined before enrollment.

6. The ECOG PS score is 0 or 1.

7. Life expectancy is at least 3 months.

8. According to RECIST 1.1, the investigators evaluated that there were measurable lesions at baseline (according to RECIST 1.1), which could be measured if they had not received local treatment such as radiotherapy (lesions located within the area of previous radiotherapy could also be selected as target lesions if progression was confirmed).

9. The function of vital organs meets the following requirements (no blood component, cell growth factor correction therapy drugs are allowed within 14 days before the first use of the study drug);

   1. Absolute neutrophil count (ANC) ≥1.5×109/L
   2. Platelet ≥100×109/L;
   3. Hemoglobin ≥9g/dL;
   4. Serum albumin ≥2.5g/dL;
   5. Total bilirubin ≤1.5 × ULN; ALT and AST≤2.5 × ULN, if there is liver metastasis, ALT and AST≤5 × ULN;
   6. Serum creatinine ≤1.5 × ULN or creatinine clearance > 60 mL/min (Cockcroft-Gault);
   7. Activated partial thromboplastin time (APTT) and International Normalized ratio (INR) ≤1.5 × ULN (for stable dose anticoagulant therapy such as low molecular weight heparin or warfarin and INR within the intended therapeutic range of anticoagulants can be screened)

10. Fertile female subjects are required to have a negative serum pregnancy test within 72 hours before the first dosing, are not breastfeeding, and use effective contraception (such as Iuds, contraceptives, or condoms) during the trial period and for at least 6 months after the last dosing of the study drug; Male subjects whose partner is a fertile woman should be surgically sterilized or agree to use effective contraception during the trial period and within 3 months after the last dose of the study drug. Sperm donation is not allowed during the study period;

Exclusion Criteria:

1. Local radiotherapy was received within 4 weeks prior to the first administration of the study drug, and adverse events due to radiotherapy have not returned to baseline levels. Participants who received palliative radiotherapy for peripheral sites (such as bone metastases) before 4 weeks may be admitted to the study, but must have recovered from any acute adverse effects;
2. Known active central nervous system (CNS) metastases and/or cancerous meningitis. Participants who have previously received BMS may participate in treatment provided they have stable BMS and have not been treated with steroids for BMS for at least 28 days prior to study start. This exception does not include cancerous meningitis, as patients with cancerous meningitis are excluded regardless of clinical stability;
3. Major surgery, open biopsy, or severe trauma occurred 28 days before the first medication;
4. Previous history of allergy to fluorouracil or irinotecan;
5. Have high blood pressure that is not well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg)
6. Subjects have poorly controlled cardiovascular clinical symptoms or diseases, including but not limited to:

(1) NYHA grade II or above heart failure; (2) unstable angina pectoris; (3) myocardial infarction within 1 year; (4) Clinically significant supraventricular or ventricular arrhythmias that remain poorly controlled without or after clinical intervention.

7. Clinically significant bleeding symptoms or definite bleeding tendency, such as gastrointestinal bleeding, hemorrhagic ulcer or vasculitis, have occurred within 3 months before the first medication.

8. Arteriovenous thrombosis events occurring within 6 months before the first medication, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, and cerebral infarction), deep vein thrombosis and pulmonary embolism, etc. Shallow vein thrombosis can be included after being determined by the researcher.

9. There is another malignant tumor that is progressing or in need of aggressive treatment, except for non-melanoma skin cancer and cervical cancer in situ for which potential treatment has been performed.

10. In the investigator's judgment, the subject has other factors that may lead to the forced termination of the study, such as other serious medical conditions (including mental illness) requiring co-treatment, serious abnormalities in laboratory test values, and family or social factors that may affect the subject's safety or the circumstances in which the trial data are collected.