Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC), and the followed maintenance treatment is an optional approach to balance the efficacy and toxicity. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib, a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously, substantially prolonged the PFS with manageable toxicity for refractory mCRC in the phase III ALTER0703 clinical trial (NCT02332499). We present updated data from the study of anlotinib plus XELOX as first-line treatment followed by anlotinib monotherapy for mCRC. Methods: In this open label, single-arm, multicenter phase II clinical trial, 29 mCRC patients without prior systemic treated, aged 18-75 and an ECOG performance status of 0 or 1 were planned to recruit. Eligible patients received capecitabine (1000 mg/m², po, d1-14, q3w) and oxaliplatin (130 mg/m², iv, d1, q3w) plus anlotinib (10mg, po, d1̃14, q3w) treatment for 6 cycles. After 6 cycles of inducing therapy, patients would receive anlotinib (12mg, po, d1̃14, q3w) as maintenance therapy until disease progression or intolerable adverse events (AEs). The primary endpoint was PFS; Secondary endpoints included ORR, DCR, DOR and safety. Results: At updated analysis (cutoff: Sep 10, 2021), a total of 27 patients were enrolled, of which 19 patients were available for efficacy assessment. In best overall response assessment, there were 63.2% PR (12/19), 26.3% SD (5/19) and 10.5% PD (2/19). The ORR was 63.2% (95% CI, 38.4-83.7%) and DCR was 89.5% (95% CI, 66.9-98.7%). One patient experienced the longest duration of treatment which was 17.5 months. The median PFS was not reached. The most common treatment related adverse events (TRAEs) of any grade (≥25%) were leukopenia, nausea/vomiting, hypertension, neutropenia, hypohemoglobinemia, hypertriglyceridemia. Grade 3/4 TRAEs (≥10%) were neutropenia (14.8%), hypertension (14.8%) and hypertriglyceridemia (11.1%). One grade 5 TRAE was pancytopenia that occurred at 2.7 months. Conclusions: The update results suggested that anlotinib combined with XELOX as first line regimen followed by anlotinib monotherapy showed promising anti-tumor activity and manageable safety for patients with mCRC. And the conclusions needed to be confirmed in randomized studies. Clinical trial information: ChiCTR1900028417.