Neoadjuvant mFOLFOXIRI Plus Bevacizumab in Patients With High-Risk Locally Advanced Rectal Cancer

Inclusion Criteria: 1. Willing and able to provide written informed consent. 2. Male or female subjects \> 18 years \< 70 of age. 3. Histological or cytological documentation of adenocarcinoma of the rectal (\<12 cm from the anal verge). 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Evaluated by pelvic contrast-enhanced MRI as having high-risk locally advanced disease: cT3 with mesorectal fascia involvement, or cT4a/b, or positive lateral lymph nodes (TNM staging reference provided). 6. No prior systemic anti-cancer therapy for colorectal cancer, including cytotoxic drugs, immune checkpoint inhibitors, molecular targeted therapy, or endocrine therapy. 7. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment 8. Willing and able to comply with the study protocol and visit schedule. Exclusion Criteria: 1. Evidence of distant metastasis (M1) confirmed by systemic CT, MRI, or PET-CT (at minimum including chest, abdomen, and pelvis). 2. Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization. 3. Complete intestinal obstruction, active bleeding, or perforation requiring emergency surgery. 4. Tumor invasion into the small intestine, or presence of intestinal fistula (including but not limited to rectovesical or rectovaginal fistula), or abscess. 5. Previous or concurrent other active malignancies, except for malignancies treated with curative intent and disease-free for \>5 years, or adequately treated carcinoma in situ. 6. Prior pelvic radiotherapy, or any anti-cancer therapy (chemotherapy, targeted therapy, hormonal therapy, immunotherapy, biologic therapy, etc.) within 12 months prior to enrollment. 7. History of thromboembolic events within 12 months prior to enrollment, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, or deep vein thrombosis. 8. Any of the following within 12 months prior to enrollment: myocardial infarction, severe/unstable angina, NYHA Class II or greater cardiac dysfunction, clinically significant supraventricular or ventricular arrhythmia, or symptomatic congestive heart failure. 9. Diagnosis of dMMR or MSI-High tumor by immunohistochemistry or PCR testing. 10. Current or within 2 weeks prior to enrollment: therapeutic antiplatelet therapy or high-dose anticoagulant therapy. 11. Major surgery (e.g., laparotomy, thoracotomy, visceral resection via laparoscopy) or severe trauma within 2 months prior to enrollment (except for colostomy performed prior to enrollment; surgical incision must be fully healed before enrollment). 12. Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). 13. Presence of interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, acute pneumonia, aneurysm, coagulation disorders, etc.). 14. Untreated active hepatitis (Hepatitis B, defined as HBV-DNA ≥500 IU/mL; Hepatitis C, defined as HCV-RNA above the lower limit of detection of the assay) or co-infection with HBV and HCV. 15. Subjects with known allergy to the study drugs or to any of its excipients. 16. Breast- feeding or pregnant women. 17. Any other severe physical or mental illness or abnormal laboratory finding that may increase the risk associated with study participation, interfere with study results, or make the patient unsuitable for the study in the investigator's judgment.