This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in combination with FOLFIRI in patients with previously treated metastatic colorectal cancer. This study includes two stages. Stage 1 is the dose-escalation stage. Once the maximum tolerated dose (MTD) of Sevacizumab has been established, additional patients will be enrolled in the cohort-expansion stage (Stage 2).

Inclusion Criteria:

• Histological/cytological confirmed unresectable metastatic colorectal cancer patients who have failed first-line oxaliplatin-based chemotherapy
• At least one measurable lesion (according to RECIST 1.1 )
• At least 4 weeks from the last chemotherapy. If patients received anti-tumor biological products, at least four t1/2 of washout period is needed
• Toxicity from previous treatment has to restore to ≤ grade 1 (NCI CTC4.0)
• ECOG performance status 0-1
• Life expectancy ≥ 3 months
• Adequate hematologic function: ANC ≥ 1.5 × 10^9 /L, HB ≥ 90 g /L (blood transfusion allowed), PLT ≥ 100 ×10^9 /L; Adequate hepatic function: ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN (patients with liver metastases ALT ≤ 5 × ULN, AST ≤ 5 × ULN); Adequate renal function: creatinine ≤ 1 × ULN; Coagulation function: INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN
• Patients of childbearing potential (male and female) must agree to use reliable methods of contraception until at least 12 weeks after the last dose
• Patients signed written inform consent
• Willingness and capability to communicate with investigators and to comply with protocol requirements

Exclusion Criteria:

• HCV, TP or HIV antibody positive
• Previously received anti-VEGF protein drugs, such as Bevacizumab,Sevacizumab
• Previously treated with irinotecan
• History of dihydropyrimidine dehydrogenase deficiency
• Patients with alcohol or drug dependence
• Participation in other clinical trials within 4 weeks before enrollment
• Active or chronic hepatitis B infection with HBV DNA > 1.0 * 10^3 IU/mL
• Serious infection requiring intravenous antibiotic therapy
• Symptomatic brain metastases
• Patients with proteinuria at screening (urine protein ≥ 1+)
• History of abdominal fistula, gastrointestinal perforation, abdominal abscess within 6 months prior to enrollment
• History of intestinal obstruction, inflammatory bowel disease, or other intestinal diseases with chronic diarrhea as the major symptom
• Serious non-healing wounds, ulcers or fractures
• Major surgery (excluding biopsy) or significant trauma within 4 weeks prior to enrollment
• Active bleeding within 3 months prior to enrollment
• Bleeding diathesis or coagulation disorder
• History of arterial or venous thrombosis
• History of myocardial infarction or stroke within 6 months prior to enrollment
• Unstable angina, congestive heart failure, New York Heart Association (NYHA) class II heart failure, uncontrollable arrhythmia, uncontrolled hypertension
• Expected to receive surgery during the study or within 1 month after the last dose
• The investigators consider the patients are not suitable for this trial
• Pregnant and lactating women
• Known allergies to any excipient in the study drug
• Patients can not complete this study for any other reason