A 63-year-old woman had recurrences of metastatic rectal cancer in the lung, peritoneum, and ovary. Regorafenib was administered at 160mg/day as third-line chemotherapy. The patient developed Grade(Gr)3 hand-foot syndrome(HFS) and Gr 2 rash, but the abdominal distension and pain were relieved by the 1st course. Analgesics could be reduced and regorafenib was administrated at reduced dosage. The patient received keishi-bukuryo-gan(EK-25)and sai-rei-tou(TJ-114) for HFS. At the beginning of therapy, ovarian metastases were not reduced and showed poor contrast enhancement on CT. Serum levels of lactate dehydrogenase(LDH)and tumor markers were increased. During the 4th course of therapy, ovarian metastases tended to shrink and serum levels of LDH and tumor markers were decreased. Ovarian metastases showed a partial response(PR)after the 6th course. Lung metastases showed a progressive disease during the 2nd course, but a PR after the 3rd course, and were not apparent after the 6th course. Reduction of metastases was maintained at 16 months after the start of therapy, and HFS was assessed at Gr 2 or lower. Physical, laboratory, and imaging findings should be carefully evaluated prior to long-term administration of regorafenib.