Liposomal Irinotecan + Oxaliplatin + Bevacizumab Versus Liposomal Irinotecan + 5-FU/LV

Inclusion Criteria:

1. Age 18 to 75 years old;
2. Patients with pancreatic cancer diagnosed by histopathology or cytology;
3. Unresectable disease assessed by multidisciplinary and imaging;
4. Subjects who have received prior failed first-line therapy, and recurrence within 6 months of the end of (neo)adjuvant therapy is considered a first-line treatment failure;
5. Subjects who have not received platinum-containing or irinotecan drugs for prior first-line therapy;
6. Patients with at least one evaluable lesion according to RECIST v1.1;
7. ECOG score of 0-2;
8. Expected survival ≥ 3 months;
9. Bone marrow function: absolute neutrophil count (ANC) ≥1.5×10\^9/L, hemoglobin ≥90 g/dL, platelets (PLT) ≥100×10\^9/L, and white blood cells (WBC) ≥3.0×10\^9/L;
10. Liver function: alanine aminotransferase (ALT), alanine aminotransferase (AST), alkaline phosphatase (ALP) ≤2.5 times the upper limit of normal (ULN), or ≤5×ULN if liver metastases are present, total bilirubin\<1.5 ULN;
11. Renal function: serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance (CCr) ≥60 mL/min (according to the Cockcroft-Gault formula);
12. Coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5 × ULN;
13. Patients with biliary obstruction should receive adequate biliary drainage; and
14. Adverse reactions arising from prior therapy must be restored to grade 1 or baseline according to CTCAE 5.0 (with the exception of toxicities such as alopecia, grade 2 or lower peripheral neuropathy, which can be enrolled with no safety risk in the judgment of the investigator);
15. Non-pregnant or lactating females; females/males of childbearing potential should use effective contraception during the study and for 6 months after completion of study treatment;
16. Patients are compliant, understand the study procedures, and sign a written informed consent form.

Exclusion Criteria:

1. Patients who have had other malignant tumors within the previous 5 years (except cured carcinoma in situ and basal cell carcinoma of the skin);
2. Uncontrollable pleural effusion or ascites;
3. Any known brain metastasis or meningeal metastasis;
4. Concomitant use of a potent CYP3A4 inducer within 3 weeks prior to the first dose, or concurrent use of a potent CYP3A4 inhibitor or potent UGT1A1 inhibitor within 3 weeks prior to the first dose;
5. Patients undergoing major organ surgery (except needle biopsy, central venous catheterization, port catheterization, stent placement for relief of biliary obstruction, percutaneous hepato-biliary drainage, cholecystostomy) or elective surgical procedures scheduled within 4 weeks prior to the first dose of study drug;
6. Systemically treated active, uncontrolled bacterial, viral, or fungal infections, defined as persistent signs/symptoms associated with the infection that do not improve despite appropriate antibiotics, antiviral therapy, and/or other treatments;
7. Subjects with congenital or acquired immunodeficiency, such as HIV-infected individuals or active hepatitis (transaminases do not meet the inclusion criteria, Hepatitis B : HBV DNA ≥ 1000 IU/ml; Hepatitis C : HCV RNA ≥ 1000 IU/ml); chronic hepatitis B viral carriers, with HBV DNA \< 2000 IU/ml, who must be concurrently receiving antiviral during the trial period treatment before enrollment;
8. Presence of serious concomitant diseases: those with diabetes mellitus that cannot be well controlled by glucose-lowering drugs, difficult-to-control hypertension, severe cardiovascular and cerebral vascular disease, renal failure, hepatic failure, uncontrolled epilepsy, central nervous system disease or history of mental disorders, those with a clear tendency to gastrointestinal bleeding, intestinal paralysis, intestinal obstruction, etc;
9. \>grade 1 diarrhea with an increase in the number of bowel movements \>4 times per day compared to baseline; moderate to severe increase in stoma discharge; limited instrumental activities of daily living or even limited spontaneous activities of daily living; life-threatening; requiring urgent treatment;
10. Those with serum albumin ≤ 3 g/dL;
11. Those who had participated in other clinical studies within 4 weeks prior to enrollment;
12. Patients assessed by the investigator to be unsuitable for participation in the trial.