Liposomal Irinotecan and Leucovorin/5-fluorouracil Plus Bevacizumab in Metastatic Colorectal Cancer

Inclusion Criteria: * Age: 18-75 years old. * Histologically or cytologically proven colon or rectum adenocarcinoma. * Confirmed as unresectable metastatic disease through radiological examination. * At least one measurable lesion (according to RECIST v1.1). * First-line treatment with oxaliplatin-based therapy. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 \~ 2. * The expected survival time ≥3 months. * Subject has adequate biological parameters as demonstrated by the following: absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count ≥100×10\^9/L, hemoglobin (Hgb) ≥90 g/L, white blood cell (WBC)≥3.0×10\^9/L. * Adequate hepatic function as evidenced by total bilirubin ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) ≤2.5 x ULN, ≤5 x ULN if liver metastases are present. * Adequate renal function as evidenced by serum creatinine (Cr)≤1.5 x ULN or creatinine clearance ≥60 mL/min, proteinuria \<2+. * Normal coagulation function (INR≤1.5). * Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening. Exclusion Criteria: * Any other malignancy within 5 years prior to randomization, with the exception of cured in-situ carcinoma or basal cell carcinoma. * Previous treatment with irinotecan/liposomal irinotecan. * MSI-H/dMMR * Massive pleural effusion or ascites requiring intervention. * Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment. * Active HIV, HBV, HCV infection. * Combined with uncontrollable systemic diseases. * Presence of severe gastrointestinal disease (including active bleeding, \> grade 1 obstruction , \> grade 1 diarrhea or gastrointestinal perforation) * History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrolment. * Presence of interstitial pneumonia or pulmonary fibrosis. * Allergy to or intolerance to therapeutic drugs or their excipients;. * History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within one month prior to enrollment. * Presence of arterial embolism, severe bleeding (excluding bleeding caused by surgery) or tendency for existing embolism or severe bleeding within 6 months before enrollment. * Patients with symptomatic central nervous system metastases. * Documented serum albumin ≤3 g/dL * Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1. * Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception. * Participated in other trial within 30 days prior to the first dose of study treatment. * Patients who had received any intravenous antineoplastic therapy within 28 days or oral antineoplastic therapy within 14 days before the first dose of study drug * Patients who are not suitable to participate in this trial for any reason judged by the investigator.