A 54-year-old woman diagnosed with sigmoid colon cancer and multiple liver metastases underwent sigmoidectomy, partial hepatectomy, and RFA in September 2009. Because of postoperative liver and lung recurrence, 5 regimens with combinations of L-OHP/CPT-11 plus anti-VEGF antibody/anti-EGFR antibody was performed. Following these treatments, she underwent hepatic arterial infusion therapy with UFT/Krestin for progressive liver metastases. Starting in November 2014, regorafenib was administered, with an immediate decrease in tumor marker levels; tumor reduction demonstrated enhanced effect against liver metastases. After 8 months of administration, we stopped regorafenib and changed to TAS-102 due to diarrhea and eating disorders. However, TAS-102 was not effective; there were significant increases in tumor markers, liver function tests, and tumor size on computed tomography, and worsening of abdominal pain. After re-administration of regorafenib, a rapid decrease in tumor marker levels and improvement of liver dysfunction and abdominal pain were observed. Re-administration continued for 8 months until best supportive care was instituted. In cases with observed therapeutic effect of regorafenib, long-term or re-administration is possible, with extension of the prognosis depending on the adjustment, and without size reduction of metastatic tumors.