In summary, we provide compelling in vitro and in vivo evidences demonstrating that m6A modification machinery in CRC, and reveal profound insights into the molecular mechanisms underlying tumorigenesis by revealing EphA2 and VEGFA were simultaneously recognized by two different binding proteins (IGF2BP2/IGF2BP3) and participated in the same signaling pathway (PI3K/Akt and ERK1/2) to jointly promote the formation of VM. Here, MAPK3 is linked to colorectal carcinoma.