Disseminated disease is present in ≈50% of colorectal cancer patients upon diagnosis, being responsible for most of cancer deaths. Addition of biological drugs, as Bevacizumab, to chemotherapy, has increased progression free survival and overall survival of metastatic colorectal cancer (mCRC) patients. However, these benefits have been only reported in a small proportion of patients. To date, there are not biomarkers that could explain the heterogeneity of this disease and would help in treatment selection. Recent findings demonstrated that microRNAs (miRNAs) play an important role in cancer and they can be encapsulated with high stability into extracellular vesicles (EVs) that are released in biological fluids. EVs can act as cell-to-cell communicators, transferring genetic information, such as miRNAs. In this context, we aimed to investigate serum EV associated miRNAs (EV-miRNAs) as novel non-invasive biomarkers for the diagnosis and prognosis of Bevacizumab-treated mCRC patients. We observed that baseline miRNA-21 and 92a outperformed carcinoembryonic antigen levels in the diagnosis of our 44 mCRC patients, compared to 17 healthy volunteers. In addition, patients who died presented higher levels of miRNA-92a and 222 at 24 weeks. However, in the multivariate Cox analysis, higher levels of miRNA-222 at 24 weeks were associated with lower overall survival. Altogether, these data indicate that EV-miRNAs have a strong potential as liquid biopsy biomarkers for the identification and prognosis of mCRC. Colorectal cancer (CRC) is the second most common cancer in women and the third most in men worldwide. Moreover, it accounts for 8.9% of all tumour-related mortality and is the second most common cause of cancer death 1. Disseminated disease is present upon diagnosis in 50% of the patients [lymph nodes (35%) and distant organs (22%)] and half of the patients diagnosed as localized tumours will eventually develop it 2. In recent years, the application of new targeted therapies, including anti-angiogenic drugs, has contributed to largely increase the overall survival (OS) of metastatic colorectal cancer mCRC patients, reporting median survivals of ≈30 months 3. Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF) has demonstrated benefits in progression-free survival (PFS) and OS in combination with chemotherapy 4,5 .