**Abstract**

In this paper, currently available systemic treatment options (regorafenib, trifluridine/tipiracil, re-challenge chemotherapy, mitomycin C plus capecitabine) for pretreated patients with metastatic colorectal cancer are discussed and compared in terms of their efficacy and safety profiles. Treatment of these patients has remained a challenge for oncologists. The evidence from clinical trials is encouraging. Knowledge of response biomarkers and/or prognostic factors may be helpful in the identification of patients who could benefit most from the treatment. Adequate medication compliance can be achieved due to awareness of toxicity risk among both physicians and cancer patients and appropriate prevention and management of adverse events.

**Keywords:** metastatic colorectal cancer, regorafenib, trifluridine/tipiracil, re-challenge chemotherapy, mitomycin C plus capecitabine
