Regorafenib and trifluridine and tipiracil hydrochloride(TFTD)have been recently used for the treatment of advanced or recurrent colorectal cancer during or after the third-line therapy. These drugs are expected to prolong survival. The progression- free survival period associated with each drug in clinical trials is known to be less than 2 months. However, reports on the overall survival in the sequential therapy with these drugs have been limited. In our institution, sequential therapy using regorafenib and TFTD has achieved longer median survival time(MST)than the previously reported. The MST with monotherapy and sequential therapy was 37 and 45 months, respectively. We currently have a patient who has not had cancer progression for 3 years and 6 months with monotherapy. Regorafenib and TFTD can potentially improve the survival time beyond our observations on monotherapy when used at the appropriate time and with a thorough understanding of their adverse effects.