Inclusion Criteria

1. Has signed the written Informed Consent Form and is capable of complying with the visit schedules and relevant procedures specified in the protocol.
2. Aged ≥ 18 years, with no restriction on gender.
3. Histologically or cytologically confirmed unresectable metastatic colorectal adenocarcinoma.
4. Has experienced treatment failure or intolerance to prior systemic standard therapies administered for metastatic disease, with failure or intolerance occurring on the most recent line of systemic therapy.
5. Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
6. Colorectal cancer characterized by proficient mismatch repair (pMMR), or microsatellite stable (MSS) status.
7. Confirmed adequate bone marrow and organ function at screening.
8. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
9. Expected survival duration ≥ 3 months.
10. Female subjects of childbearing potential, or male subjects whose partners are females of childbearing potential, agree to strictly use effective contraceptive measures throughout the treatment period and for 6 months after treatment completion. Lactating female subjects agree to completely refrain from breastfeeding throughout the treatment period and for 6 months after treatment completion.

Exclusion Criteria

1. Prior disease progression, treatment intolerance, or contraindication to all three agents: fruquintinib, trifluridine/tipiracil (TAS-102), and regorafenib.
2. Prior receipt of immunotherapy targeting anti-PD-(L)-1 or PD-L2.
3. History of severe toxicities related to anti-PD-(L)-1 immunotherapy or anti-VEGF therapy that necessitated permanent discontinuation of treatment, or contraindication to any of the above agents.
4. Prior administration of interleukin (IL)-2 or IL-15 cytokines.
5. Absence of documented clear evidence to confirm left- or right-sided primary colorectal tumor; or presence of primary colorectal lesions on both sides.
6. Radiologically confirmed active or symptomatic central nervous system (CNS) metastases, including intraparenchymal brain, leptomeningeal, and spinal cord metastases.
7. Subjects with unresolved adverse events attributable to any prior anti-tumor therapy that have not recovered to NCI CTCAE (Version 5.0) Grade 0 or Grade 1, or returned to baseline levels prior to randomization. Exceptions include alopecia, fatigue, hypothyroidism managed solely with thyroid hormone replacement, hyperglycemia controlled exclusively by insulin replacement, electrolyte abnormalities manageable with symptomatic treatment only, and other conditions judged by the Investigator to pose no safety risks with study drug administration.
8. History of another malignant tumor within 5 years before the first dose of study drug. The following malignancies are allowed if curatively resected, with no current evidence of residual or recurrent disease and an extremely low recurrence risk: carcinoma in situ, cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, lentigo maligna, localized prostate cancer, papillary thyroid carcinoma, non-invasive papillary urothelial carcinoma.
9. Active autoimmune disease requiring systemic therapy (e.g., disease-modifying anti-rheumatic drugs, corticosteroids, immunosuppressants) within 2 years prior to the first study drug dose. Replacement therapies (e.g., thyroxine, insulin, physiological corticosteroids for adrenal or pituitary insufficiency) shall not be regarded as systemic immunosuppressive treatment.
10. Prior history of interstitial lung disease, pulmonary fibrosis, pneumoconiosis, drug-induced pneumonitis, radiation pneumonitis, or other pulmonary disorders requiring corticosteroids or other therapeutic intervention.
11. Active uncontrolled bleeding or known bleeding diathesis;
12. Known history of allogeneic solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
13. Subjects with known or suspected hypersensitivity to the study drug or any of its excipients.
14. Female subjects who are pregnant, breastfeeding, or planning to conceive before study drug administration, during treatment, or within 6 months after the last study drug dose.
15. Any past medical condition, prior treatment, or abnormal laboratory findings, or current clinical evidence that, in the Investigator's judgment, may compromise subject safety, interfere with the acquisition of informed consent, impair subject compliance, or confound the safety evaluation of the study drug; subjects with psychiatric disorders, altered mental status, or substance abuse that impairs the ability to comprehend the informed consent process and/or complete required study assessments; subjects whom the Investigator determines will fail to comply with protocol requirements for known or foreseeable reasons.