PurposeTo assess the efficacy and safety of regorafenib versus rechallenge chemotherapy in previously treated mCRC patients in third-line setting.Materials and methodsThe data of 104 patients diagnosed with mCRC enrolledfrom2010to2017 in six oncology centers were analyzed. Tumor treatment options were obtained from follow-up and treatment files. Rechallenge chemotherapy was identified as the re-use of the regimen which was previously administered to patients in one of the therapy lines and obtained disease control, these were the patients whose disease did not progress within 3months.ResultsA total of 104 patients had received previously two lines of chemotherapy regimens for mCRC. Of these, 73 patients with mCRC who received regorafenib and 31 those who received rechallenge chemotherapy in third-line therapy were analyzed. Overall survival was better with rechallenge than it was with regorafenib (HR 0.29 95% CI 0.16-0.54, p<0.001). Median OS was 12.0months (95% CI 8.1-15.9) in rechallenge versus 6.6months (95% CI 6.0-7.3) in regorafenib group (p<0.001). Progression-free survival in the rechallenge group showed a higher median value of 9.16months (95% CI 7.15-11.18) versus with that recorded in the regorafenib group of 3.41months (95% CI 3.01-3.82), in favor of rechallenge chemotherapy. The most common adverse events of regorafenib was liver function test abnormality and hand-foot syndrome. Although grade 3 or 4 adverse events were similar, non-hematologic toxicities were more common than those of rechallenge.ConclusionsRechallenge is still a valuable option against regorafenib in patients who achieved disease control in one of the first two lines of therapy. Even though mCRC patients treated with regorafenib benefited clinically from this treatment, we revealed that chemotherapy rechallenge compared to regorafenib was more effective in the third-line treatment for mCRC patients.