This is a prospective, single-arm clinical study designed to evaluate the 6-month progression-free survival rate (6-month PFS rate) of Doxorubicin liposome combined with CapOX and Bevacizumab regimen as first-line treatment for advanced colorectal adenocarcinoma with SMAD4R361H/C mutation. The study plans to recruit 13 patients. After receiving 8 cycles of induction therapy, patients whose efficacy is evaluated as complete response (CR), partial response (PR), or stable disease (SD) (according to RECIST 1.1) will enter maintenance therapy.

Inclusion Criteria:

1. The patient voluntarily participates in the study, signs the informed consent form, and demonstrates good compliance;
2. Age 18 years or older (inclusive), regardless of gender;
3. Histologically and/or cytologically confirmed unresectable colorectal adenocarcinoma;
4. For left-sided colon cancer or rectal cancer patients, must be non-RAS wild-type;
5. Non-dMMR/MSI-H;
6. SMAD4R361H/C mutation;
7. No prior history of systemic chemotherapy;
8. ECOG performance status of 0 or 1;
9. Hematological tests (within 14 days without blood transfusion): neutrophil absolute count ≥ 1.5 × 10⁹/L, platelet count ≥ 100 × 10⁹/L, hemoglobin ≥ 90 g/L;
10. Liver function tests (AST and ALT ≤ 3 × ULN, bilirubin ≤ 1.5 × ULN; if liver metastasis is present, AST and ALT ≤ 5 × ULN);
11. Renal function (serum creatinine ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 60 mL/min);
12. Both male and female subjects of reproductive age must use effective contraception.

Exclusion Criteria:

1. Patients with known contraindications to Doxorubicin liposome, Oxaliplatin, Capecitabine, or Bevacizumab;
2. Patients who have received radiotherapy or any anti-tumor treatments (chemotherapy, targeted therapy, immunotherapy, radiofrequency ablation, traditional Chinese medicine with anti-tumor indications, immunomodulators, or tumor embolization, etc.);
3. Patients who have had other malignancies within the past 5 years or have concurrent malignancies (except for cured skin basal cell carcinoma and carcinoma in situ of the cervix);
4. Patients who have experienced significant clinical bleeding symptoms, obvious bleeding tendency, or hemoptysis within 3 months prior to treatment, or who have had venous/thrombotic events such as cerebrovascular accidents (including transient ischemic attacks, intracerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism within the previous 6 months; or require long-term anticoagulation treatment with warfarin or heparin, or require long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day);
5. Patients with active cardiovascular diseases within 6 months before treatment, including myocardial infarction, severe/uncontrolled angina. Echocardiography showing left ventricular ejection fraction <50%, or poorly controlled arrhythmia;
6. Known history of primary immunodeficiency virus infection;
7. Patients with active or uncontrolled severe infections;
8. Any other disease, clinically significant metabolic abnormalities, physical examination abnormalities, or laboratory test abnormalities, and based on the investigator's judgment, there is reasonable suspicion that the patient has a condition or disease that is unsuitable for the use of the study drug;
9. Any situation that, in the investigator's opinion, could pose a risk to the patient receiving study drug treatment, interfere with the assessment of the study drug's safety, or affect the interpretation of results.