Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the world. More than half of all CRC patients will eventually develop metastases and require treatment accordingly, but few validated predictive factors for response to systemic treatments exist. In order to ascertain which patients benefit from specific treatments, there is a strong need for new and reliable biomarkers. We conducted a comprehensive search using the PUBMED database, up to December 2019, in order to identify relevant studies on predictive biomarkers for treatment response in metastatic CRC. We will herein present the currently used and potential biomarkers for treatment response and bring up-to-date knowledge on the role of circulating microRNAs, associated with chemotherapy and targeted therapy regimens used in metastatic CRC treatment. Molecular, tumor-related, disease-related, clinical, and laboratory predictive markers for treatment response were identified, mostly proposed, with few validated. Several circulating microRNAs have already proven their role of prediction for treatment response in CRC, but future clinical studies are needed to confirm their role as biomarkers across large cohorts of patients.