Diffractive multispectral optical imaging plays an essential role in optical sensing, which typically suffers from the image blurring problem caused by the spatially variant point spread function. Here, we propose a novel high-quality and efficient hybrid space calibrated 3D network “HSC3D” for spatially variant diffractive multispectral imaging that utilizes the 3D U-Net structure combined with space calibration modules of magnification and rotation effects to achieve high-accuracy eight-channel multispectral restoration. The algorithm combines the advantages of the space calibrated module and U-Net architecture with 3D convolutional layers to improve the image quality of diffractive multispectral imaging without the requirements of complex equipment modifications and large amounts of data. A diffractive multispectral imaging system is established by designing and manufacturing one diffractive lens and four refractive lenses, whose monochromatic aberration is carefully corrected to improve imaging quality. The mean peak signal-to-noise ratio and mean structural similarity index of the reconstructed multispectral images are improved by 3.33 dB and 0.08, respectively, presenting obviously improved image quality compared with a typical Unrolled Network algorithm. The new algorithm with high space calibrated ability and imaging quality has great application potential in diffraction lens spectroscopy and paves a new method for complex practical diffractive multispectral image sensing.