Nowadays, colorectal cancer is the fourth most common type of tumor all over the world. When diagnosed, approximate to 50%-60% of tumors have metastasized, thus resulting in a grim prognosis. Chemotherapy is regarded as standard treatment for patients with colorectal cancer, however, limitations of chemotherapy cannot be ignored, such as low selectivity, insufficient concentrations in tumor tissues, and systemic toxicity. Recently, six targeted drugs have been approved by the U.S. Food and Drug Administration (FDA) for treatment of metastatic colorectal cancer (mCRC), including bevacizumab, aflibercept, regorafenib, cetuximab, and panitumumab. The development of these drugs marked significant advancement in the field of mCRC therapy. The addition of biologic agents to chemotherapy has prolonged the median overall survival. Now, many investigational drugs are under clinical trials, of which programmed death (PD)-1/L1 has drawn much attention. In this review, new biologic agents under clinical trials such as MEK/MET/RAS/RAF/PD-1 inhibitors with potentials for mCRC treatment are concluded by describing targeted drugs approved by FDA, to offer new insights into global trends and future development.