The mesh-less method abandons the idea of traditional mesh method. In numerical calculation, it only needs the node information, and it's not necessary to connect nodes into mesh cells. Aiming at the problem of non-equilibrium chemical reaction flows in a threedimensional muzzle with moving boundaries, this paper proposed a three-dimensional least squares mesh-less (3D-LSM) algorithm, and the ALE (Arbitrary Lagrangian-Eulerian) form multi-component Euler governing equations were adopted for fluid dynamics modeling; then, a finite-rate reaction model was used to deal with the chemical reactions in the flow field, a time-division method was applied to solve the stiff problem of chemical reactions, and multi-component AUFS (artificially upstream flux vector splitting) format was introduced to calculate the convective flux term of the governing equation. In addition, the weighted-point filling strategy and the dynamic point cloud method were employed to deal with the topological structure changes in the point clouds caused by the large displacement movement of the projectile in the three-dimensional muzzle flow field. Finally, the proposed mesh-less method was applied to calculate the muzzle of a 12.7mm gun, and accurately captured the bottle-shaped shock wave structure in the complex muzzle flow field and the second muzzle flame phenomenon; the calculation results were compared with the experimental results and obtained a good match, which had proved the feasibility of the proposed 3D-LSM method. The research findings of this paper provided a new solution for the simulation of high-speed non-equilibrium reaction jets with multicomponent and large-displacement moving boundaries.