Dose Escalation and Expansion Clinical Trial of Irinotecan Liposome Combined With Oxaliplatin and 5-FU/LV Plus Bevacizumab as First-line Treatment of Metastatic Colorectal Cancer

Inclusion Criteria: * 18-75 years old. * Histopathologically confirmed patient with an inoperable metastatic colorectal adenocarcinoma. * The unresectable stage of metastatic disease has not received any systemic antitumor therapy. * For subjects previously receiving neoadjuvant or adjuvant therapy, the date of first discovery of disease progression must be at least 12 months removed from the date of last administration of neoadjuvant or adjuvant therapy. * The presence of at least 1 measurable lesion that can be evaluated according to the RECIST v1.1 criteria. * ECOG 0 * Normal bone marrow and organ function: ① Neutrophils (ANC) ≥1.5×10\^9/L, platelets (PLT) ≥100×10\^9/L, hemoglobin (Hb) ≥90g/L, white blood cells (WBC) ≥3.0×10\^9/L, albumin (ALB) ≥35 g/L, and no bleeding tendency; ② AST, ALT and alkaline phosphatase (ALP) were all ≤2.5× upper limit of normal range (ULN), and ≤5×ULN when liver metastases occurred; The total bilirubin level doesn't exceed the upper limit of the agency's normal range; Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 ml/min (calculated according to Cockroft-Gault) * Understand the situation of this study, patients and/or legal representatives voluntarily agree to participate in this study and sign informed consent form. Exclusion Criteria: * Patients with known MSI-H or dMMR who were evaluated by investigators as suitable for treatment with immune checkpoint inhibitors. * Patients allergic to the investigational drug and its excipients. * Underweight (body mass index \[BMI\]\<18.5 kg/m\^2). * Known or suspected central nervous system metastasis. * Received irinotecan before enrollment. * Had undergone surgery and other oncologic treatments within the first 4 weeks of enrollment. * Previous treatment-related toxicity didn't return to NCI-CTCAE v5.0 class I or below. * The use of CYP3A, CYP2C8, and UGT1A1 inhibitors or inducers couldn't be discontinued or were not discontinued within 2 weeks prior to enrollment. * Serious gastrointestinal disorders. * Interstitial lung disease. * Tendency of arterial embolism and massive bleeding within 6 months before enrollment (except surgical bleeding). * Patients with fluid accumulation that couldn't reach a stable state and small amount of pleural effusion or ascites on imaging without clinical symptoms could be enrolled. * Intestinal obstruction, signs and symptoms of intestinal obstruction, or the stent has been previously implanted and the stent has not been removed before the screening period. * Gastrointestinal perforation, intraperitoneal abscess, and fistula. * Any serious or uncontrolled systemic disease, including uncontrolled high blood pressure, heart disease, active bleeding, active viral infection, etc. * Have had other malignancies within the past 5 years or currently, except cured cervical carcinoma in situ, uterine carcinoma in situ, and non-melanoma skin cancer. * Patients of childbearing age who refuse to take contraceptives, women who are pregnant or breastfeeding. * The researchers didn't consider it appropriate to participate in this study.