**1. Introduction**

To this date, management of heavily pretreated patients with metastatic colorectal cancer, who present with good performance status and adequate organ function reserve, constituted a challenge for oncologists. However, two anticancer therapies dedicated for this specific group of patients became available nowadays. One of them is regorafenib, an oral inhibitor of protein kinases associated with angiogenesis. Another one is trifluridine/tipiracil (TAS-102), an orally administered combination of a thymidine-based nucleic acid analog, and tipiracil hydrochloride, a thymidine phosphorylase inhibitor. Treatment with both anticancer agents contributed to a significant improvement of overall survival (OS) and progressionfree survival (PFS) in randomized III phase studies of Caucasian (CORRECT and TERRA) and Asian patients (CONCUR and RECOURSE). Recently, clinical benefits associated with administration of both drugs and good tolerability thereof were also confirmed in an observational study, REGOTAS. The aim of currently ongoing trials is to evaluate the efficacy and safety of regorafenib and TAS-102 combined with other anticancer drugs in metastatic colorectal cancer patients. While preliminary results of some of those studies seem promising, more evidence is needed to formulate any clinically relevant conclusions.

Another treatment option in metastatic colorectal cancer is re-induction of previously used chemotherapy with oxaliplatin- or irinotecan-based regimens.

## *Multidisciplinary Approach for Colorectal Cancer*

Importantly, the time elapsed since completion of the primary treatment to the re-induction should not be shorter than 9 months. Finally, patients with metastatic colorectal cancer can receive chemotherapy with mitomycin C plus capecitabine. This generally neglected treatment option seems particularly reasonable in the case of countries in which regorafenib and trifluridine/tipiracil have been registered but are not reimbursed.

The aim of this review paper is to discuss the therapeutic options that could be used in metastatic colorectal cancer patients after three or more lines of systemic therapy.
