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PURPOSE Established that the only approved agents in previously treated metastatic colorectal cancer (CRC) are trifluoridine/tipiracil and regorafenib, we conducted a systematic review of all the published phase 2-3 trials, with the scope to evaluate the benefit of any later-line regimens in refractory metastatic CRC. METHODS Phase 2-3 studies that enrolled patients with stage IV disease receiving salvage therapies for refractory CRC were identified using electronic databases (Pubmed, EMBASE, and Cochrane Library). Clinical outcomes were p