Metastatic colorectal cancer (mCRC) is the third leading cause of cancer deaths worldwide. Median overall survival (OS) of patients with metastatic colorectal cancer (mCRC) has reached up to 30 months in recent clinical trials of frst line therapies. Following disease progression after the standard in both, 1st and 2nd line, combination chemotherapy with monoclonal antibodies, many patients maintain a good performance status and a signifcant proportion is motivated to undergo further therapy. Choices of treatment beyond the second line setting for mCRC are therefore becoming increasingly important. At the same time, longer life expectancy increases the number of elderly patients with colorectal cancer (CRC) potentially in need of oncology treatment. Unfortunately, elderly patients (≥65... years) often go untreated and they are also under-repre-sented in clinical trials. Yet there is some evidence suggesting that ‘ft’ elderly patients havesimilar outcomes and tolerance to chemotherapy treatment to their younger counterparts. The evidence supporting the administration of new targeted therapies in patients older than 65 years is scarce and more research is needed. Recently, new options have entered the therapeutic feld of treatment of mCRC beyond-line: Regorafenib is a multikinase inhibitor approved for mCRC patients who have progressed on chemotherapy (including fuoropyrimidines, irinotecan, and oxaliplatin), plus VEGF inhibitor(s) and – if RAS wild-type – an anti-EGFR inhibitor. Regorafenib signifcantly improved OS, compared to placebo, in two phase III trials (CORRECT and CONCUR) in mCRC patients. Trifuridine/Tipiracil, an oral fuoropyrimidine, also resulted in signifcantly improved OS when compared to place- bo in the phase III RECOURSE trial, which was conducted in a similar patient population to CORRECT. However, the toxicity profle of TAS-102, substantially less impacting on the quality of life of the elderly patient and more manageable, makes it a valid therapeutic option compared to regorafenib in this setting of patients. In this paper, we review all the available data concerning the use of therapies for mCRC beyond second-line in patients older than 65 years of age and discuss the differences between this age subgroup and younger patients.