The combination of targeted therapeutic agents for metastatic colorectal cancer (mCRC) salvage treatment has potential in clinics. Here this group conducts a single-arm, open-label, phase II trial assessing the combination therapy of regorafenib (tyrosine kinase inhibitor) and sintilimab (PD-1 targeting) as a safe and effective salvage-line treatment for mCRC patients who have progressed upon second-line treatment.