Liposomal Irinotecan Plus Bevacizumab in Irinotecan-refractory Metastatic Colorectal Cancer

Inclusion Criteria: 1. Age: ≥18 years old； 2. Histopathologically and/or cytologically confirmed unresectable metastatic colorectal adenocarcinoma； 3. Previous treatment with irinotecan , and have progression of disease during treatment or within three months thereafter； 4. At least one measurable lesion (according to RECIST v1.1)； 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 \~ 1； 6. The expected survival time ≥3 months； 7. Adequate bone marrow function : no blood transfusion and/or use of increasing leukocyte drugs (excluding oral medication) within 14 days prior to enrollment Absolute neutrophil count (ANC) ≥1.5×109/L Platelet count ≥100×109/L Hemoglobin (Hgb) ≥90 g/L； 8. Adequate hepatic function as evidenced by: Total bilirubin ≤1.5 × upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, ≤5 × ULN if liver metastases are present. Serum albumin ≥30 g/L； (9Adequate renal function as evidenced by: serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance ≥60 mL/min. proteinuria\<2+（those with proteinuria ≥2+ at baseline had to demonstrate ≤1 g protein per 24 hours）； (10)Coagulation function: International normalised ratio (INR) ≤1.5, activated partial thromboplastin time (APTT) ≤1.5 × ULN； (11)Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening； Exclusion Criteria: 1. Any other malignancy within 5 years, with the exception of cured in-situ carcinoma or basal cell carcinoma etc； 2. Patients with the primary lesion located in the left colon and RAS/BRAF wild-type who did not use cetuximab on the first-line； 3. Patients with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR)； 4. Massive pleural effusion or ascites requiring intervention； 5. Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment； 6. Active HIV infection； 7. Combined with uncontrollable systemic diseases within 6 months before the first administration； 8. Presence of severe gastrointestinal disease； 9. History of major surgery (such as laparotomy, thoracotomy or intestinal resection) within 28 days before the first administration,or plan to undergo major surgery during the study period； 10. Presence of interstitial pneumonia or pulmonary fibrosis； 11. History of allergy or hypersensitivity to drug or any of their excipients； 12. History of pulmonary hemorrhage/hemoptysis ≥Grade 2 (defined as bright red blood of at least 2.5mL) within one month before the first administration； 13. Presence of arterial embolism, severe bleeding (excluding bleeding caused by surgery) or tendency for existing embolism or severe bleeding within 6 months before the first administration； 14. Combined symptomatic brain metastasis, meningeal metastasis, spinal cord tumor invasion, and spinal cord compression syndrome； 15. Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1 within 14 days before the first administration； 16. Participate in other study and use study drug within 1 month or within 5 half-lives of the drug (whichever comes first) before the first administration； 17. Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception； 18. Patients who are not suitable to participate in this trial for any reason judged by the investigator；